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Biomedicines
Special Issues
Targeting the Hedgehog Signaling Pathway in Cancer
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Targeting the Hedgehog Signaling Pathway in Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 6661

Special Issue Editor

Dr. Maja Sabol

E-Mail Website
Guest Editor
Laboratory for Hereditary Cancer, Division of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croatia
Interests: Hedgehog signaling; melanoma; ovarian cancer; prostate cancer; HNSCC

Special Issue Information

Dear Colleagues,

The Hedgehog signaling pathway is an evolutionarily conserved signaling pathway crucial for embryonic development and tissue patterning. It is mostly inactive in the differentiated tissues of adult organisms, except in the stem cell compartment. It regulates many cellular processes, such as proliferation, differentiation, epithelial-mesenchymal transition and stem cell maintenance.

Hedgehog signaling is frequently upregulated in various cancers, and this can occur via different mechanisms depending on the tumor type. While some tumors are clearly associated with mutations in pathway components or epigenetic regulation, in others, the mechanisms are more complex and often depend on the tumor microenvironment and the tumor–stroma communication. Regardless of the mechanism, activation of the Hedgehog pathway is associated with cancer cell proliferation, survival and metastasis, as well as drug resistance. Additional complexity in Hedgehog signal transduction is added by the non-canonical signal transduction, which can activate the pathway independently of the ligand binding/membrane components, and by the cross-talk with other signaling pathways. This makes Hedgehog signaling an interesting therapeutic target in cancer.

This Special Issue focuses on the role of Hedgehog signaling in cancer, its cross-talk with other signaling pathways and its potential as a diagnostic, prognostic and therapeutic target.

Dr. Maja Sabol
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Hedgehog signaling
  • GLI proteins
  • Hedgehog signaling inhibitors
  • non-canonical signaling
  • cancer stem cells
  • drug resistance
  • targeted cancer therapy
  • tumor microenvironment
  • primary cilia
  • epithelial-mesenchymal transition

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Published Papers (2 papers)

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19 pages, 2402 KiB  
Article
Signaling Switching from Hedgehog-GLI to MAPK Signaling Potentially Serves as a Compensatory Mechanism in Melanoma Cell Lines Resistant to GANT-61
by Nikolina Piteša, Matea Kurtović, Nenad Bartoniček, Danai S. Gkotsi, Josipa Čonkaš, Tina Petrić, Vesna Musani, Petar Ozretić, Natalia A. Riobo-Del Galdo and Maja Sabol
Biomedicines 2023, 11(5), 1353; https://doi.org/10.3390/biomedicines11051353 - 3 May 2023
Cited by 2 | Viewed by 2347
Abstract
Background: Melanoma represents the deadliest skin cancer due to its cell plasticity which results in high metastatic potential and chemoresistance. Melanomas frequently develop resistance to targeted therapy; therefore, new combination therapy strategies are required. Non-canonical signaling interactions between HH-GLI and RAS/RAF/ERK signaling were [...] Read more.
Background: Melanoma represents the deadliest skin cancer due to its cell plasticity which results in high metastatic potential and chemoresistance. Melanomas frequently develop resistance to targeted therapy; therefore, new combination therapy strategies are required. Non-canonical signaling interactions between HH-GLI and RAS/RAF/ERK signaling were identified as one of the drivers of melanoma pathogenesis. Therefore, we decided to investigate the importance of these non-canonical interactions in chemoresistance, and examine the potential for HH-GLI and RAS/RAF/ERK combined therapy. Methods: We established two melanoma cell lines resistant to the GLI inhibitor, GANT-61, and characterized their response to other HH-GLI and RAS/RAF/ERK inhibitors. Results: We successfully established two melanoma cell lines resistant to GANT-61. Both cell lines showed HH-GLI signaling downregulation and increased invasive cell properties like migration potential, colony forming capacity, and EMT. However, they differed in MAPK signaling activity, cell cycle regulation, and primary cilia formation, suggesting different potential mechanisms responsible for resistance occurrence. Conclusions: Our study provides the first ever insights into cell lines resistant to GANT-61 and shows potential mechanisms connected to HH-GLI and MAPK signaling which may represent new hot spots for noncanonical signaling interactions. Full article
(This article belongs to the Special Issue Targeting the Hedgehog Signaling Pathway in Cancer)
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Review

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23 pages, 3053 KiB  
Review
Modulation of Hedgehog Signaling for the Treatment of Basal Cell Carcinoma and the Development of Preclinical Models
by Meghan W. Dukes and Thomas J. Meade
Biomedicines 2022, 10(10), 2376; https://doi.org/10.3390/biomedicines10102376 - 23 Sep 2022
Cited by 5 | Viewed by 3803
Abstract
Basal Cell Carcinoma (BCC) is the most commonly diagnosed cancer worldwide. While the survivability of BCC is high, many patients are excluded from clinically available treatments due to health risks or personal choice. Further, patients with advanced or metastatic disease have severely limited [...] Read more.
Basal Cell Carcinoma (BCC) is the most commonly diagnosed cancer worldwide. While the survivability of BCC is high, many patients are excluded from clinically available treatments due to health risks or personal choice. Further, patients with advanced or metastatic disease have severely limited treatment options. The dysregulation of the Hedgehog (Hh) signaling cascade drives onset and progression of BCC. As such, the modulation of this pathway has driven advancements in BCC research. In this review, we focus firstly on inhibitors that target the Hh pathway as chemotherapeutics against BCC. Two therapies targeting Hh signaling have been made clinically available for BCC patients, but these treatments suffer from limited initial efficacy and a high rate of chemoresistant tumor recurrence. Herein, we describe more recent developments of chemical scaffolds that have been designed to hopefully improve upon the available therapeutics. We secondly discuss the history and recent efforts involving modulation of the Hh genome as a method of producing in vivo models of BCC for preclinical research. While there are many advancements left to be made towards improving patient outcomes with BCC, it is clear that targeting the Hh pathway will remain at the forefront of research efforts in designing more effective chemotherapeutics as well as relevant preclinical models. Full article
(This article belongs to the Special Issue Targeting the Hedgehog Signaling Pathway in Cancer)
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